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PubMed1977

[Scientific theoretical models in dentistry].

Developments leading to modern medicine only began about 150 years ago. The foundation of this progress was laid by the introduction of scientific working methods into practical and theoretical medicine. The principal methodical procedures are described in the present work, defined and examined as to its scientific basis. Examples from dental, oral, and maxillo-facial surgery are given as proof that the models used in the definition of present day biological research are helpful not only give accuracy to content recognized by scientific method but also to assure transition from theoretical to practical science.

Dental Articulators↗

PubMed1999

Relaxed replication of mtDNA: A model with implications for the expression of disease.

Heteroplasmic mtDNA defects are an important cause of human disease with clinical features that primarily involve nondividing (postmitotic) tissues. Within single cells the percentage level of mutated mtDNA must exceed a critical threshold level before the genetic defect is expressed. Although the level of mutated mtDNA may alter over time, the mechanism behind the change is not understood. It currently is not possible to directly measure the level of mutant mtDNA within living cells. We therefore developed a mathematical model of human mtDNA replication, based on a solid foundation of experimentally derived parameters, and studied the dynamics of intracellular heteroplasmy in postmitotic cells. Our simulations show that the level of intracellular heteroplasmy can vary greatly over a short period of time and that a high copy number of mtDNA molecules delays the time to fixation of an allele. We made the assumption that the optimal state for a cell is to contain 100% wild-type molecules. For cells that contain pathogenic mutations, the nonselective proliferation of mutant and wild-type mtDNA molecules further delays the fixation of both alleles, but this leads to a rapid increase in the mean percentage level of mutant mtDNA within a tissue. On its own, this mechanism will lead to the appearance of a critical threshold level of mutant mtDNA that must be exceeded before a cell expresses a biochemical defect. The hypothesis that we present is in accordance with the available data and may explain the late presentation and insidious progression of mtDNA diseases.

Alleles↗

PubMed1998

Presentation and reading level of sleep brochures: are they appropriate for sleep disorders patients?

OBJECTIVE: Sleep-disorders patients must be given information and health education they understand. The purpose of this study was twofold: (1) to assess suitability of American Sleep Disorders Association and National Sleep Foundation patient education brochures; and (2) to assess one widely used brochure, using patient input and patient literacy level, as a model for development of future materials. DESIGN: Twelve American Sleep Disorders Association and National Sleep Foundation brochures were assessed for reading level using Grammatik, and for design, presentation, and motivating qualities using the Suitability Assessment of Materials (SAM). Patient literacy level was assessed using the Rapid Estimate Of Adult Literacy in Medicine (REALM). SETTING: The Louisiana State University Medical Center sleep clinic, faculty private sleep clinic, and in the sleep center laboratory. PATIENTS OR PARTICIPANTS: During the months of February-May 1997, 170 sleep disorders patients, 39% African American, 59% white participated in the study. Participants ranged in age from 18-73 years, with a mean age of 46. MEASUREMENTS AND RESULTS: Suitability scores for the 12 brochures indicate that none scored in the superior range, 83% scored adequate, and 17% scored not suitable. Ninety-four percent of the brochures were written on a 12th grade level or higher, yet 37% of the sleep patients tested were reading at less than a 9th grade level. Low-level readers were significantly more likely than their higher-reading-level counterparts to report that a brochure was too long (22% vs 12%; p < .05), and that they would need help reading it (44% vs 3%; p < .001). CONCLUSIONS: Patients need sleep information given to them on a level they understand. When developing and selecting appropriate materials, reading level, length, and suitability of written material should be considered.

Adolescent↗

PubMedDate not supplied

The state of the art of the zebrafish model for toxicology and toxicologic pathology research--advantages and current limitations.

The zebrafish (Danio rerio) is now the pre-eminent vertebrate model system for clarification of the roles of specific genes and signaling pathways in development. The zebrafish genome will be completely sequenced within the next 1-2 years. Together with the substantial historical database regarding basic developmental biology, toxicology, and gene transfer, the rich foundation of molecular genetic and genomic data makes zebrafish a powerful model system for clarifying mechanisms in toxicity. In contrast to the highly advanced knowledge base on molecular developmental genetics in zebrafish, our database regarding infectious and noninfectious diseases and pathologic lesions in zebrafish lags far behind the information available on most other domestic mammalian and avian species, particularly rodents. Currently, minimal data are available regarding spontaneous neoplasm rates or spontaneous aging lesions in any of the commonly used wild-type or mutant lines of zebrafish. Therefore, to fully utilize the potential of zebrafish as an animal model for understanding human development, disease, and toxicology we must greatly advance our knowledge on zebrafish diseases and pathology.

Animals↗

PubMed2004

Doctors' views about the importance of shared values in HIV positive patient care: a qualitative study.

Robert Veatch has proposed a model of the doctor-patient relationship that has as its foundation the sharing of values between the doctor and the patient. This paper uses qualitative research conducted with six doctors involved in the long term, specialised care of HIV positive patients in South Australia to explore the practical application of Veatch's value sharing model in that setting. The research found that the doctors in this study linked "values" with sexual identity such that they defined value sharing, in part, as a shared set of values and beliefs about sexual identity and practices. They voluntarily identified themselves as either homosexual or heterosexual and they regarded the relation between their own sexual identity and that of their patients as important for the provision of quality care. None of the doctors thought that value sharing, in the way they defined it, was essential to the clinical relationship, but the homosexual doctors attributed a greater degree of importance to it than their heterosexual colleagues.

Ethics, Clinical↗

PubMed2005

Modeling psychological empowerment among youth involved in local tobacco control efforts.

The American Legacy Foundation funded 13 state health departments for their Statewide Youth Movement Against Tobacco Use in September 2000. Its goal was to create statewide tobacco control initiatives implemented with youth leadership. The underlying theory behind these initiatives was that tobacco control efforts can best be accomplished by empowering youth. To evaluate these initiatives, the authors developed a conceptual framework for youth empowerment that was used as a guide in developing standardized cross-site measures. This article describes the domains and attributes used to operationalize psychological empowerment as an outcome of youth involvement in these initiatives and presents results of our two-stage structural equation modeling. We conclude with a summary of lessons learned to date and recommendations for applying these findings to work in the field.

Adolescent↗

PubMed1993

Psychological and behavioral consequences of job loss: a covariance structure analysis using Weiner's (1985) attribution model.

B. Weiner's (1985) attribution model of achievement motivation and emotion was used as a theoretical foundation to examine the mediating processes between involuntary job loss and employment status. Seventy-nine manufacturing employees were surveyed 1 month prior to permanent displacement, and finding another job was assessed 18 months later. Covariance structure analysis was used to evaluate goodness of fit and to compare the model to alternative measurement and structural representations. Discriminant validity analyses indicated that the causal dimensions underlying the model were not independent. Model predictions were supported in that internal and stable attributions for job loss negatively influenced finding another job through expectations for re-employment. These predictions held up even after controlling for influential unmeasured variables. Practical and theoretical implications are discussed.

Adaptation, Psychological↗

PubMed2006

Codon usage and selection on proteins.

Selection pressures on proteins are usually measured by comparing homologous nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a novel method, termed volatility, to estimate selection pressures on proteins on the basis of their synonymous codon usage (Plotkin and Dushoff 2003; Plotkin et al. 2004). Here we provide a theoretical foundation for this approach. Under the Fisher-Wright model, we derive the expected frequencies of synonymous codons as a function of the strength of selection on amino acids, the mutation rate, and the effective population size. We analyze the conditions under which we can expect to draw inferences from biased codon usage, and we estimate the time scales required to establish and maintain such a signal. We find that synonymous codon usage can reliably distinguish between negative selection and neutrality only for organisms, such as some microbes, that experience large effective population sizes or periods of elevated mutation rates. The power of volatility to detect positive selection is also modest--requiring approximately 100 selected sites--but it depends less strongly on population size. We show that phenomena such as transient hyper-mutators can improve the power of volatility to detect selection, even when the neutral site heterozygosity is low. We also discuss several confounding factors, neglected by the Fisher-Wright model, that may limit the applicability of volatility in practice.

Algorithms↗

PubMed1991

Native herpes simplex virus glycoprotein D vaccine: immunogenicity and protection in animal models.

Mice, guinea pigs, and rhesus monkeys were immunized with immunoaffinity-purified native glycoprotein D (gD) derived from herpes simplex virus type 1 (HSV1). The native glycoprotein has evoked significant in vivo responses even at low doses. Thus, mice immunized with doses as low as 1 microgram were significantly protected from the morbidity and mortality of lethal HSV2 challenge and from establishment of latent HSV2 infection. Protection was dose-related and correlated with prechallenge serum neutralizing antibody titres to HSV. Similarly, immunized guinea-pigs demonstrated significant reductions in the frequency, severity and duration of genital lesions induced by HSV2 vaginal challenge. In long term immunogenicity studies, immunized rhesus monkeys exhibited significant serum neutralizing antibody responses to both HSV1 and HSV2. In vitro stimulation of monkey peripheral blood leucocytes with purified gD resulted in a significant cellular proliferative response. The results obtained in these animal models with a gD subunit vaccine provide an appropriate foundation for the initiation of human studies.

Animals↗

PubMed2002

Beyond effectiveness: the evaluation of information systems using A Comprehensive Health Technology Assessment Framework.

A Comprehensive Health Technology Assessment Framework is presented as a conceptual tool for decision-making about health technologies, including information technologies. The aim of the model is to provide an empirical, evidence-based foundation for health technology decisions. The major framework dimensions are (1) population at risk, (2) population impact, (3) economic concerns, (4) social context (including ethical, legal, and political concerns), and (5) technology assessment information. This multi-disciplinary approach provides guidelines on use of appropriate information in aligning 'stakeholder wants' and 'population needs'.

Decision Making, Organizational↗

PubMedDate not supplied

A confirmatory factor analysis of the Caregiving Appraisal Scale for caregivers of home-based ventilator-assisted individuals.

OBJECTIVE: To confirm the underlying dimensions of the Caregiving Appraisal Scale (CAS) with use of data collected from caregivers of home-based ventilator-assisted individuals (VAIs). DESIGN: Cross-sectional survey. SETTING: Residences of home-based VAIs. SAMPLE: Two hundred seventy-seven primary family caregivers of VAIs. MEASURES: Twenty-eight-item CAS developed by Lawton et al. (1989), and an investigator-developed instrument to assess physical health and sociodemographic characteristics of both VAIs and their caregivers. INTERVENTION: None. ANALYSIS: Confirmatory factor analysis with principal components extraction. An oblique (oblimin) solution was used for rotation of the factor matrices. The number of common factors needed to obtain the best fit of the factor model was determined with use of maximum-likelihood estimation. Confirmatory factor analysis with linear structural equation modeling was also performed. RESULTS: Confirmatory factor analysis did not fully replicate the factor structure proposed by Lawton et al. CONCLUSIONS: The model proposed by Lawton et al. provides a useful foundation for examining the appraisal of family caregivers of home-based VAIs. Additional development work is needed for the CAS.

Adult↗

PubMed1992

Motor activity and the mesotelencephalic dopamine function. I. High-resolution temporal and genetic analysis of open-field behavior.

In a genetic selection experiment whose goal was to construct congenic neurological animal model lines with different mesotelencephalic dopamine systems, we produced foundation F2 generations derived from crosses (C57BL/6ByJXBALB/cJ and C57BL/6ByJXCXBI/ByJ) between highly inbred mouse lines with different dopamine systems. In this report, temporal distribution, latency, and genetic variability of open-field (OF) behavioral variables were investigated in order to establish a behavioral profile for the various generations and to provide behavioral data as a first step towards multivariate studies on correlations between OF behaviors and mesencephalic and striatal tyrosine hydroxylase activity. Analysis of the behavioral data provided evidence that measures of the open-field behaviors varied significantly across time segments of the test and that the temporal profiles of several behavioral variables were genotype-dependent. It is suggested that (1) OF behaviors have dynamic temporal profiles, and (2) temporal-genetic analysis can be a useful auxiliary method in the functional interpretation of behavior.

Animals↗

PubMed2001

Anterior chamber stability during bimanual irrigation and aspiration. Theoretical and experimental analysis.

PURPOSE: To determine the requirements for maintaining a stable anterior chamber during bimanual irrigation and aspiration (I/A) using side-port cannulas. SETTING: Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. METHODS: A theoretical fluid dynamic model of the closed I/A system was developed. Model predictions were compared with experimental flow measurements made on the Alcon Legacy 20000 system using a number of commercial and custom I/A cannulas. RESULTS: Bore diameter, length, and orifice size determine the pressure-flow relationship of cannulas. Four of 18 tested irrigation cannulas were able to maintain anterior chamber stability when used with a 23-gauge/0.3 mm orifice aspiration cannula and maximum aspiration settings. All 4 had a 21-gauge lumen diameter. A shorter cannula length also contributed to higher flow. CONCLUSIONS: Anterior chamber stability during bimanual I/A required the irrigation system to have lower flow resistance than the aspiration system, which can be provided by using cannulas with larger lumen diameters and shorter lengths. Special cannula designs can provide these characteristics without requiring larger side-port incisions.

Anterior Chamber↗

PubMed1998

The international development of the RGHQoL: a quality of life measure for recurrent genital herpes.

This paper describes the international development and psychometric testing of the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL), a condition-specific quality of life (QoL) instrument. The theoretical foundation for the measure is the needs-based model of QoL and the content of the instrument was derived from in-depth qualitative interviews with relevant patients in the UK. Versions of the RGHQoL were required for the UK, USA, Italy, Germany, France and Denmark for use in international clinical trials. The results indicate that the final 20 item measure has good reliability, internal consistency and validity for all language versions. A small responsiveness study in Denmark suggested that the measure is sensitive to changes in QoL associated with the initiation of suppression treatment for recurrent genital herpes (RGH). It is concluded that the RGHQoL is a valuable instrument for inclusion in clinical trials. The psychometric properties of the instrument are such that it may also be used to monitor the progress of individual patients.

Adult↗

PubMed2003

Social work and spiritual counseling: results of one state audit.

Interdisciplinary care is the foundation of hospice service for the terminally ill. This model of care includes a holistic focus on the patient and family, including not only physical and medical management but also psychological and spiritual needs. The importance of social issues is acknowledged and supported through federal and state regulations requiring social work and spiritual counseling services as a part of the hospice care team. State regulatory reports were analyzed to identify compliance issues for social workers and spiritual counselors within hospice programs in a midwestern state. Problems with care planning, assessment, and bereavement services were identified in this process. Deficiencies point to the opportunities for social work educators to improve the training of future hospice social workers and the challenges involved in training spiritual counselors.

Bereavement↗

PubMed2003

Waiting for organ transplantation: results of an analysis by an Institute of Medicine Committee.

One of the most visible and contentious issues regarding the fairness of the original system of organ procurement and allocation is the argument that it resulted in great disparities in the total amount of time a patient waited for an organ (i.e. the time from registration at a transplantation center to transplant), depending on where he or she lived. In an attempt to resolve this debate, Congress charged the National Academy of Sciences, Institute of Medicine to perform an independent study of the original system and proposed rule changes. In an analysis of approximately 68,000 transplant waiting list records, the committee developed several conclusions and recommendations largely specific to liver transplantation policies. The purpose of this paper is to describe both the results of the study and the statistical foundations of the mixed-effects multinomial logistic regression model that led to the committee's conclusions.

Adolescent↗

PubMed1986

Thoughts on the treatment of schizophrenia.

The author contends that the clinical relationship is the foundation for treating the person with schizophrenia. However, the models and scientific data available to the clinician have been limited by prevailing ideologies. Despite important contributions from interpersonal, pharmacologic, and rehabilitation treatment perspectives, each has curtailed the range of clinical observation and the capacity for integration of treatments. Even recent advances in clinical science methodology have contributed to a short fall in treatment knowledge. The author espouses a broad medical model for defining the range of data and integration of techniques relevant to therapeutics. He views phenomenology as the crucial concept for clinical exploration, and contrasts this approach with the shallowness of purely descriptive approaches on the one hand and the distortion imposed by theoretical presentiments of psychotherapy on the other. Continuity of care and integration of therapies can emerge from phenomenology in the context of the clinical relationship.

Antipsychotic Agents↗

PubMed2002

Effects of early cerebral malaria on cognitive ability in Senegalese children.

Twenty-nine Senegalese children with a history of cerebral malaria (CM) performed more poorly on the Kaufman Assessment Battery for Children (K-ABC) Simultaneous Processing domain and on the Test of Variables of Attention (TOVA) attention capacity indicators in comparison with a matched control group. Thus, CM can disrupt neuropsychological integration during critical developmental periods, impacting on global neurological integrity, attentional vigilance, perceptual acuity, and subsequent development of visual-spatial processing and memory foundational to global cognitive ability. A subsequent structural equation model confirmed that rural children are at greater risk for CM, subsequent attention deficits, and other developmental risk factors in addition to the CM impact on K-ABC performance. We document CM as one of a host of developmental risk factors within the complex web of poverty in sub-Saharan Africa, which limit children's ability to achieve their full intellectual potential and, thus, extend the human cost of the disease beyond general measures of mortality and morbidity.

Brain Edema↗